Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Unlabelled: This study aims to assess the role of methotrexate-related gene polymorphisms in children with acute lymphoblastic leukemia (ALL) during high-dose methotrexate (HD-MTX) therapy and to explore their effects on serum metabolites before and after HD-MTX treatment. The MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435C>T, and GSTP1 313A>G genotypes of 189 children with ALL who received chemotherapy with the CCCG-ALL-2020 regimen from January 2020 to April 2023 were analyzed, and toxic effects were reported according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Fasting peripheral blood serum samples were collected from 27 children before and after HD-MTX treatment, and plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The results of univariate and multivariate analyses showed that MTHFR 677C>T and ABCB1 3435 C>T gene polymorphisms were associated with the delayed MTX clearance (P < 0.05) and lower platelet count after treatment in children with MTHFR 677 mutation compared with wild-type ones (P < 0.05), and pure mutations in ABCB1 3435 were associated with higher serum creatinine levels (P < 0.05). No significant association was identified between MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435 C>T, and GSTP1 313A>G genes and hepatotoxicity or nephrotoxicity (P > 0.05). However, the serum metabolomic analysis indicated that the presence of the MTHFR 677C > T gene polymorphism could potentially contribute to delayed MTX clearance by influencing L-phenylalanine metabolism, leading to the occurrence of related toxic side effects.
Conclusion: MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene.
Trial Registration: This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/ ).
What Is Known: • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear.
What Is New: • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00431-023-05267-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Methylenetetrahydrofolate reductase (MTHFR) 677C>T rs1801133 genetic variant, homocysteine, folate, and vitamin B12 levels in patients with multiple sclerosis: a scoping review.
Mult Scler Relat Disord
August 2025
Clinical and Laboratory Pathophysiology Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil; Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil; Pontifical Catholic University of Para
Background: The MTHFR 677C>T rs1801133 genetic variant, homocysteine (Hcy), cyanocobalamin (vitamin B12), and folic acid (vitamin B9) are factors associated with the physiopathology of multiple sclerosis (MS). This scoping review discussed the relationship between MTHFR 677C>T rs1801133 variant, Hcy, vitamin B12, and folate levels with the susceptibility and pathophysiology of MS.
Methods: PubMed/US National Library of Medicine/USA database were used to search for cross-sectional, case-control, systematic reviews, and meta-analysis studies published in Portuguese and English, from 1990 to 2025.
Effects of Gender Differences in 677C > T and Homocysteine Level on the Occurrence of Adverse Pregnancy Outcomes.
Int J Genomics
August 2025
Department of Medical Genetic Center of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), People's Hospital of Henan University, Zhengzhou, Henan, China.
The MTHFR 677C > T polymorphism in women has been associated with an increased risk of deep venous thrombosis and adverse pregnancy outcomes (APOs). However, research concerning its effects in men remains limited. This study examined 662 adults with a history of pregnancies affected by chromosomal abnormalities (CAs: 343 females and 319 males), 137 adults with a history of pregnancies affected by cleft lip and palate (CLP: 71 females and 66 males), and 133 adults with a history of biochemical pregnancies (BPs: 65 females and 68 males), forming three case groups.
View Article and Find Full Text PDFLow Dietary Folate Increases Developmental Delays in the Litters of Mice.
Nutrients
August 2025
Departments of Human Genetics and Pediatrics, McGill University, Montreal, QC H3A 0C7, Canada.
: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice.
View Article and Find Full Text PDFMolecular landscape of non-driver genes in myeloproliferative neoplasms through 333 cancer genes panel: Insights to reveal in Pakistan.
BMC Med Genomics
August 2025
Department of Medical Biology, University of Québec at Trois-Rivieres, Trois-Rivieres, Québec, G9 A 5H7, Canada.
Background: Discoveries of driver mutations in myeloproliferative neoplasms (MPNs) have filled the diagnostic gap however there are non-driver genes which play an important role in the phenotype of the disease. This study is the first to evaluate the molecular landscape of non-driver genes in MPNs patients from Pakistan.
Methods: A sample of fourteen MPNs patients (eight essential thrombocythemia, five primary myelofibrosis and one polycythemia vera) was investigated by the next generation sequencing, using 333 cancer genes panel.
Retinal vascular dysfunction in the Mthfr mouse model of cerebrovascular disease.
Alzheimers Dement
August 2025
The Jackson Laboratory, Bar Harbor, Maine, USA.
Introduction: Investigations of retinal biomarkers for Alzheimer's disease (AD) and AD and related dementias (ADRD), has increased significantly. We examine retinal vascular health in a mouse containing the ADRD risk variant Mthfr to determine if changes in retina mirror similar changes in cerebrovasculature.
Methods: Morphology and function of retinal vasculature and neurons were assessed using in vivo imaging, immunohistochemistry, and pattern electroretinography.